Gene Imaging for Studying Pharmacokinetics of Gene in Vivo at the Real Time

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The aim of this study was to develop the gene imaging for studying where the mRNA is located, how much it overexpress, and how it is distributed by using the nuclear medicine modality. Human epidermoid carcinoma cell line; KB-31, its mdr1 transfected cell line; KB-G2, and human thyroid tumor; TCO-1 which overexpress mdr1, were used throughout the in vitro and in vivo studies.1. Antisense DNA (AS) and sense DNA (S) were labeled with Tc-99m under supervised by Dr. Donald J Hnatowich (Professor, University Massachusetts Medical School), and then they were incubated with KB-31, KB-G2 and TCO-1 cells. We found AS-accumulations occurred by the antisense mechanism.2. Gene imaging was successfully obtained when Tc-99m-AS was injected into the KB-G2 tumor implanted into the thigh of mice. This is the first report of antisense imaging in the world.3. Tc-99m-AS was accumulated specifically into the KB-G2 tumors when it was injected into mice intravenously, but its accumulation was not high enough to get the image.4. Transfecting agents such as jetPEI, Neophectin and Chariot enhanced the accumulation of Tc-99m-AS into KB-G2 cells with 3-8-fold comparing with the naked AS-DNAs, but these increases were not observed significantly in vivo study.5. Nanoparticles consisting of Tc-99m-Streptavidine-TAT-AS were prepared by our unique methods and these showed the higher accumulations into the cell comparing with naked AS-DNAs. In vivo studies are now undergoing.